Schaaf-Yang syndrome: Clinical phenotype and effects of 4 years of growth hormone treatment.

INTRODUCTION: Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder caused by truncating mutations of the MAGEL2 gene, located in the Prader-Willi syndrome (PWS) region. PWS and SYS have phenotypic overlap. Patients with SYS are often treated with growth hormone (GH), but evidence for the effectiveness of the treatment in patients with SYS is limited.

METHODS: This study describes 7 children with SYS. We studied their phenotype, genotype, and the effect of GH-treatment on height and BMI during four years and on body composition during one year.

RESULTS: All patients had a normal birth weight. Most patients had hypotonia and feeding difficulties after birth (86%). Full-scale IQ ranged from <50 to 92. All patients above the age of 2 years had psycho-behavioral problems. There were no apparent correlations between the phenotype and the location of the defect in the MAGEL2 gene. Mean (95% CI) height SDS increased significantly from -1.74 (-3.55;0.07) at start to -0.05 (-1.87;1.77) after four years of GH-treatment. Mean (95% CI) BMI SDS decreased significantly from 2.01 (1.02;3.00) to 1.22 (0.18;2.26) after six months and remained the same during the rest of the follow-up. Fat mass percentage SDS decreased and lean body mass did not change during one year of treatment in three patients.

CONCLUSION: Patients presented with a phenotype of hypotonia, respiratory insufficiency and feeding difficulties after birth, endocrine disorders, intellectual disability and behavioral problems. Treatment with GH significantly improved height SDS and BMI over the course of 4 years.